Therapeutic Advances in Medical Oncology最新文献

Background: Docetaxel, following progression on immunotherapy and platinum-based chemotherapy, remains the standard of care for advanced non-small-cell lung cancer (NSCLC) but offers limited promise. Antibody-drug conjugates (ADCs) may improve outcomes in this population.

Objectives: Data from the literature, mainly randomized controlled trials (RCTs), have shown discrepancies. This report evaluates the efficacy and safety of ADCs versus docetaxel in previously treated advanced NSCLC.

Design: The systematic review and meta-analysis was conducted focusing on phase II/III RCTs to synthesize available evidence regarding efficacy outcomes and safety of ADCs compared to docetaxel.

Data resources and methods: Databases (PubMed (MEDLINE), EMBASE, and Cochrane Library), clinical trial registries, and proceedings of global oncology conferences from January 2015 to November 2024 were screened comparing ADC versus docetaxel. Two researchers independently completed data retrieval and screening work using Covidence. The Cochrane Risk of Bias Tool (RoB 2.0) was used to assess the methodological quality of the included RCTs. The primary outcomes include progression-free survival (PFS) and overall survival (OS), while the secondary outcomes include objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). The pooled hazard ratios (HRs) and odds ratios (ORs) were meta-analyzed using the appropriate generic variance and Mantel-Haenszel methods. Random-effect models were used to compute pooled estimates.

Results: Of the 212 records screened, three RCTs involving 1597 patients were included. ADCs did not significantly improve PFS (pooled HR: 0.91, 95% CI: 0.73-1.13). For OS, the pooled HR was 0.88 (95% CI: 0.78-1.00, p = 0.06), reflecting a borderline significant trend favoring ADCs, with negligible heterogeneity (I ² = 0%). Furthermore, subgroup analysis demonstrated a significant OS benefit in the nonsquamous cohort (HR: 0.85, 95% CI: 0.74-0.98, p = 0.03). In addition, no difference was observed in ORR (OR: 1.16, 95% CI: 0.54-2.51) and DCR (OR: 1.39, 95% CI: 0.75-2.57). Grade ⩾ 3 treatment-related AEs were significantly lower (pooled OR: 0.49, 95% CI: 0.26-0.90, p = 0.02) with ADCs, despite high heterogeneity (I ² = 87%).

Conclusion: Overall, there was no difference between the docetaxel and the ADC treatment arms; however, our findings report a significant survival benefit in the subgroup of patients with nonsquamous NSCLC pathology treated with ADCs compared to docetaxel with a manageable safety profile. Further research is needed to address heterogeneity, refine patient selection, and obtain more mature survival data with predictive biomarkers.

Background: Neoadjuvant chemotherapy (NAC) plays a central role in the management of early breast cancer (BC), offering prognostic information and improving surgical outcomes. Blood-based biomarkers, including inflammatory markers-such as neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR)-and circulating nucleic acids-such as circulating tumor DNA (ctDNA), cell-free DNA (cfDNA), and cfDNA integrity index (cfDI)-have been investigated for their potential to predict treatment response.

Objectives: To systematically evaluate the prognostic value of inflammatory indices and circulating nucleic acids measured during NAC for predicting pathological complete response (pCR) in early BC.

Design: Systematic review with qualitative synthesis.

Data sources and methods: Twenty-four studies were included, examining changes in NLR, PLR, ctDNA, cfDNA, and cfDI during NAC. Study quality was assessed using the Newcastle-Ottawa Scale, and the strength of evidence was evaluated with a qualitative GRADE approach. Due to heterogeneity in biomarker definitions, sampling timepoints, and statistical methods, data were synthesized narratively.

Results: A reduction in PLR from baseline to mid-NAC (ΔPLR <0) was consistently associated with higher pCR rates. ctDNA clearance, particularly at mid- and post-NAC, was frequently linked to increased pCR and better overall survival. In contrast, findings on NLR dynamics were inconsistent. Evidence for cfDNA and cfDI was limited and mixed, with some studies suggesting lower cfDNA and higher cfDI may be associated with improved outcomes. Variability in biomarker thresholds and timepoints was a common limitation.

Conclusion: Mid-NAC PLR decrease and ctDNA clearance show moderate evidence as predictors of pCR and may help guide treatment decisions. The prognostic value of NLR, cfDNA, and cfDI remains uncertain and requires further prospective, standardized investigation.

Background: Breast phyllodes tumors (PT) are rare fibroepithelial tumors classified by the World Health Organization into benign, borderline, and malignant subtypes. Although surgery is the primary treatment, local recurrence remains a concern. The role of postoperative radiotherapy (PORT) in improving local control remains unclear.

Objectives: This study aimed to investigate the effect of PORT in patients with borderline PT (BoPT) and malignant PT (MPT) after R0 resection (complete resection without tumor margins) and to identify prognostic factors related to local recurrence-free survival (LRFS) and overall survival (OS).

Design: This was a retrospective multicenter study.

Methods: We retrospectively evaluated patients with BoPT and MPT who underwent R0 resection between January 2002 and October 2023. Propensity score matching was used to balance the covariates between the PORT (n = 37) and non-PORT (n = 83) groups. Kaplan-Meier curves were used to estimate the 5-year LRFS and OS, while Cox regression analyses were used to identify prognostic factors. Subgroup analysis was used to assess the potential benefits of radiotherapy.

Results: Of 480 patients, 438 (91.25%) underwent surgery alone and 42 (8.75%) received PORT. PORT did not improve the LRFS or OS. After matching, 5-year LRFS (71.42% vs 70.17%, p = 0.58) and OS (82.41% vs 80.02%, p = 0.82) were similar between the groups. Multivariate analysis of matched samples showed that axillary lymph node metastasis was significantly associated with LRFS and OS. Malignant heterologous elements were independent poor prognostic factors for LRFS. No subgroup benefited from radiotherapy.

Conclusion: In our study, PORT did not significantly improve LRFS or OS in patients with BoPT and MPT. Key prognostic factors may guide treatment decisions in these patients.

Background: Despite significant advancements in treatment, patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) continue to face the challenge of drug resistance, highlighting the need to develop new drugs and treatment strategies. Pyrotinib has exhibited notable efficacy in managing HER2-positive MBC, especially in individuals with brain metastasis (BM). However, real-world evidence on the effectiveness of pyrotinib re-treatment remains limited.

Objectives: This study aims to assess the efficacy of pyrotinib re-treatment-including treatment beyond progression (TBP) and rechallenge-in patients with HER2-positive MBC, particularly those with BMs, in a real-world clinical setting.

Design: A retrospective, multicenter, real-world study.

Methods: Patients with HER2-positive MBC who experienced progression during pyrotinib treatment and subsequently continued or resumed pyrotinib-based regimens were enrolled. Patients were divided into two groups according to the re-treatment pattern: the pyrotinib TBP group and the pyrotinib rechallenge group. The endpoints were progression-free survival (PFS) and overall survival (OS).

Results: A total of 226 participants received pyrotinib TBP, whereas 33 received pyrotinib rechallenge. The median PFS of pyrotinib re-treatment (7.2 vs 6.3 months, p = 0.31) and the median OS, measured from the start of pyrotinib re-treatment (31.6 vs 21.0 months, p = 0.062), were comparable between the two groups. Among patients with BMs before pyrotinib re-treatment, the median PFS for pyrotinib re-treatment was 7.2 months, and the median OS was 25.2 months.

Conclusion: Pyrotinib TBP and pyrotinib rechallenge both demonstrate potential benefits for patients with HER2-positive MBC, including those with BM.

Background: Regorafenib targets tumor angiogenesis and oncogenic signaling by inhibiting multiple kinases involved in angiogenesis, oncogenesis, and the tumor microenvironment. Chemotherapy of FOLFIRI causes direct cytotoxic damage to tumor cells.

Objectives: We evaluated the efficacy and safety of regorafenib plus FOLFIRI with uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) genotyping-guided irinotecan dose escalation in patients with metastatic colorectal cancer (mCRC) who had received second- or third-line systemic therapy.

Design: A total of 153 patients were randomized (at a ratio of 2:1) to receive either regorafenib plus FOLFIRI (experimental group, 102 patients) or regorafenib alone (control group, 51 patients).

Methods: Both groups received regorafenib (120 mg daily) for 21 consecutive days in 28-day cycles. In addition, the experimental group received FOLFIRI with UGT1A1 genotyping-guided irinotecan dose escalation. The primary outcome was progression-free survival (PFS). The secondary outcomes were overall survival (OS), disease control rate (DCR), and adverse events.

Results: The final cohort included 116 patients. The experimental group exhibited significant improvement in PFS (p = 0.016) but marginally significant improvements in DCR (p = 0.055). Specifically, PFS improved significantly for experimental group patients carrying wild-type rat sarcoma virus (RAS; p = 0.003) and those carrying left-sided colon tumors (p = 0.015). A trend toward improved OS was noted in experimental group patients carrying wild-type RAS (p = 0.096). No significant between-group difference was observed in the incidence of severe adverse events (all p > 0.05).

Conclusion: Our findings suggest that regorafenib plus FOLFIRI significantly improved PFS in patients with mCRC and offers a safety profile similar to that of regorafenib alone. This regimen may be particularly beneficial for patients with mCRC carrying wild-type RAS and those carrying left-sided tumors. However, larger phase III randomized controlled trials are necessary to confirm the efficacy and safety of this combination therapy before adoption into standard practice.

Trial registration: ClinicalTrials.gov registry: NCT03880877 (https://clinicaltrials.gov/search?cond=NCT03880877).

Background: Alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II) are classical tumor markers in clinical practice. However, the relationship between tumor markers and prognosis in hepatocellular carcinoma (HCC) patients receiving immune checkpoint inhibitor (ICI) therapy remains unclear.

Objectives: This study aims to explore the prognostic value of AFP and PIVKA-II in HCC patients treated with ICIs.

Design: This study was a single-center, retrospective investigation aimed to assess the prognostic value of AFP and PIVKA-II in HCC patients receiving immune checkpoint inhibitors.

Methods: This retrospective study included HCC patients who received ICIs treatment at Wuhan Union Hospital between July 2020 and March 2024. Serum AFP and PIVKA-II levels were collected before treatment. Patients were stratified into two groups based on AFP ⩾ 400 μg/L (yes = 1, no = 0) and PIVKA-II ⩾ 40 mAU/mL (yes = 1, no = 0). A total of 61% (114/186) of patients scored ⩽ 1, while 39% (72/186) scored 2. The objective response rate (ORR) and disease control rate (DCR) were calculated for both groups. Kaplan-Meier survival curves and Cox regression models were used to analyze overall survival (OS) and progression-free survival (PFS). Receiver operating characteristic curves were generated to demonstrate the predictive ability of combined independent prognostic factors for long-term survival.

Results: The cohort consisted of 186 patients, divided into the low-risk group (n = 114) and the high-risk group (n = 72). Among all patients, 34.4% (64/186) achieved complete or partial response. Concurrent elevation of AFP and PIVKA-II was inversely associated with ORR (p = 0.012). The high-risk group exhibited significantly shorter OS (adjusted HR: 2.226 (95% CI: 1.410-3.513); p < 0.001) compared to the low-risk group. The integrated model combining AFP, PIVKA-II, and Barcelona Clinic liver cancer stage demonstrated moderate to good predictive capability for long-term risk stratification, with time-dependent area under the curves of 0.78 (9-month), 0.68 (12-month), and 0.63 (15-month).

Conclusion: Concurrent elevation of AFP and PIVKA-II is significantly associated with shorter survival outcomes in HCC patients following ICI therapy.

Background: Liver metastases (LM) in advanced non-small-cell lung cancer (NSCLC) are associated with poor clinical outcomes. The tolerogenic immune microenvironment in the liver may contribute to inferior response to immune checkpoint inhibitors (ICIs). We hypothesized that the presence of LM may be associated with an expanded peripheral myeloid population, using the neutrophil-to-lymphocyte ratio (NLR) as a surrogate in patients treated with ICIs.

Objectives: We evaluated the impact of LM and NLR on clinical outcomes in patients with advanced NSCLC treated with ICIs.

Design: This was a retrospective analysis conducted at a single cancer center.

Methods: We reviewed the records of 324 patients with advanced NSCLC treated with programmed death ligand-1 (PD-L1) inhibitors as monotherapy or in combination with cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibitors. Clinical outcomes, including progression-free survival (PFS) and overall survival (OS), were evaluated among patients with and without LM in NLR-High (NLR ⩾ 5) and NLR-Low (NLR < 5) subgroups.

Results: Patients with LM had significantly higher median NLR compared to patients without LM (median 7.3 vs 4.5, p < 0.001). Patients with LM had significantly shorter median PFS (HR 1.54, p = 0.006) and median OS (HR 1.56, p = 0.014). Patients with LM who were NLR-High (LM+ NLR-H) had shorter median PFS and median OS (2.0 months and 5.4 months, respectively) compared to patients who had LM and were NLR-Low (LM+ NLR-L, median PFS 4.0 months and median OS 13.3 months). This trend was also observed within the PD-L1 > 50% subgroup. In 42 patients with evaluable response and LM, 25/42 (59.5%) of patients had concordant responses in the liver and extra-hepatic sites.

Conclusion: Patients with LM who are NLR-High had the poorest clinical outcomes to ICI, and this appeared to be irrespective of PD-L1 status. Ongoing translational work will provide further insight into tumor myeloid subpopulations that may correlate with treatment resistance.

Solitary fibrous tumours (SFT) are fibroblastic mesenchymal tumours that can develop virtually at any site. It usually affects adults, and its incidence is estimated as 1 new case per million people per year. SFT is characterized by a gene fusion involving NAB2 (NGFI-A-binding protein 2) and STAT6 (signal transducer and activator of transcription 6); a higher nuclear STAT6 immunostaining can be seen in SFT cells, and it is considered an excellent marker for immunohistochemical diagnosis. The 2020 WHO classification defines two categories for SFT: intermediate (rarely metastasizing) and malignant. Many risk stratification models have been proposed to predict the behaviour of these tumour identities. In case of localized SFTs, the cornerstone of the treatment remains surgery with the aim of negative margins (R0) when technically feasible. In intermediate/high-risk SFTs with positive margins (R1/R2) with no possibility to re-resection or in meningeal high-risk SFTs, adjuvant radiotherapy (RT) could be performed. Neoadjuvant RT could also have a role in both extra-meningeal and meningeal localizations. Sole RT could have a role in managing non-resectable SFTs even in a curative intent. Medical therapy plays an important role in the metastatic/advanced SFTs. Conventional chemotherapy may be used, with doxorubicin and dacarbazine being active though yielding poor responses. Other active drugs with currently ongoing studies in SFT are eribulin and trabectedin. Antiangiogenetic treatments have also been shown to provide benefit in this histological subtype. An area of recent investigation is immunotherapy, with an ongoing randomized trial comparing nivolumab + ipilimumab versus pazopanib in advanced rare soft tissue sarcomas, including SFTs. Despite its rarity and therefore the difficulty in performing prospective randomized trials with a large number of patients, many promising results in perioperative (radiotherapy) or in the metastatic (medical therapy) setting have been obtained. This review overviews the main characteristics and provides the current knowledge on standard therapies.

Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths in Germany. National data on the management of HCC remain scarce.

Objectives: This study aims to provide an up-to-date overview of clinical characteristics, treatment modalities, and survival outcomes among patients with HCC in Germany.

Design: This is a real-world retrospective study using health insurance data from BARMER.

Methods: Patients with an HCC diagnosis between 2016 and 2020 were identified in the BARMER database. Comorbidities, anticancer therapies, and treatment pathways of those patients were evaluated using descriptive statistics and survival analysis.

Results: A total of 2778 patients with HCC were identified. Of these, 1569 (56.5%) received any anticancer therapy. Transarterial chemoembolization (TACE; 22.3%), liver resection (LR; 20.9%), and systemic therapy (18.9%) were the most frequently used approaches. Survival varied significantly, with liver transplantation (LTx) offering the best outcomes, with a 5-year survival rate of 76%, followed by LR with 40%. Treatments with curative intent, including LTx, LR, and ablation, had a median survival of 40.4 months, compared to 9.7 months for non-curative modalities.

Conclusion: In Germany, a substantial proportion of HCC patients remain untreated. Therapies with curative intent, particularly transplantation, provide relevant survival benefits. Improving surveillance efforts could enhance the proportion of patients eligible for these modalities and may represent a critical step toward improved outcomes for patients with HCC.

Dedifferentiated ovarian carcinomas (DDOC) are rare and aggressive malignancies characterized by a mixture of differentiated and undifferentiated tumor components, often associated with poor prognosis. This case report describes a 55-year-old woman initially diagnosed with early-stage high-grade endometrioid ovarian carcinoma who experienced rapid disease progression during adjuvant platinum-based chemotherapy, culminating in death within 4 months. Retrospective molecular analyses revealed pathogenic variants in the SMARCA4 gene, leading to a revised diagnosis of DDOC. The tumor exhibited resistance to conventional chemotherapy, highlighting the challenges associated with managing this aggressive tumor subtype. In our case, molecular profiling identified two potentially targetable alterations: biallelic SMARCA4 loss and a pathogenic PIK3CA mutation, both of which may inform future therapeutic strategies. This case underscores the importance of integrating molecular diagnostics into routine practice for accurate classification and highlights the urgent need for personalized treatment strategies, including targeted and immunotherapy options, for this formidable tumor subtype.